BRDT

Bromodomain, testis-specific
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsBRDT ; BRD6; CT9
External IDsOMIM: 602144 MGI: 1891374 HomoloGene: 21064 IUPHAR: 2729 ChEMBL: 1795185 GeneCards: BRDT Gene
Orthologs
SpeciesHumanMouse
Entrez676114642
EnsemblENSG00000137948ENSMUSG00000029279
UniProtQ58F21Q91Y44
RefSeq (mRNA)NM_001242805NM_001079873
RefSeq (protein)NP_001229734NP_001073342
Location (UCSC)Chr 1:
92.41 – 92.48 Mb		Chr 5:
107.33 – 107.39 Mb
PubMed search

Bromodomain testis-specific protein is a protein that in humans is encoded by the BRDT gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family.[1][2]

BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene.[2] The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids [3][2]

Model organisms

Model organisms have been used in the study of BRDT function. A conditional knockout mouse line, called Brdttm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[7] Homozygous mutant males were sub-fertile and both sexes had a decreased number of lumbar and sacral vertebrae.[7]

Role in male contraceptive medication

BET inhibitors such as JQ1 block the region of BRDT responsible for chromatin binding, and cause a reversible reduction of sperm production, sperm quality, and size of the testis in mice.[15] The mechanism of action of JQ1 could be explained by considering Brdt’s functions as a driver of testis-specific gene expression and post-meiotic chromatin reorganization [3][2] As BET inhibitors also inhibit other BET proteins BRD2, BRD3, and BRD4, they are likely to have effects in people beyond temporary male sterility.

References

  1. ↑ Jones MH, Numata M, Shimane M (Jan 1998). "Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh". Genomics 45 (3): 529–34. doi:10.1006/geno.1997.5000. PMID 9367677.
  2. ↑ 2.0 2.1 2.2 2.3 "Entrez Gene: BRDT bromodomain, testis-specific".
  3. ↑ 3.0 3.1 Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S, Hery P, Jounier S, Depaux A, Vitte AL, Guardiola P, Pernet K, Debernardi A, Lopez F, Holota H, Imbert J, Wolgemuth DJ, Gérard M, Rousseaux S, Khochbin S (2012). "Bromodomain-dependent stage-specific male genome programming by Brdt". EMBO J 31 (19): 3809–20. doi:10.1038/emboj.2012.233. PMID 22922464.
  4. ↑ "Radiography data for Brdt". Wellcome Trust Sanger Institute.
  5. ↑ "Salmonella infection data for Brdt". Wellcome Trust Sanger Institute.
  6. ↑ "Citrobacter infection data for Brdt". Wellcome Trust Sanger Institute.
  7. ↑ 7.0 7.1 7.2 7.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  8. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  9. ↑ "International Knockout Mouse Consortium".
  10. ↑ "Mouse Genome Informatics".
  11. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  12. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  13. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  14. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  15. ↑ "A male contraceptive pill in the making?". 16 August 2012. Retrieved 17 August 2012.

Further reading